TY - JOUR T1 - Deficiency in Protein <span class="sc">l</span>-Isoaspartyl Methyltransferase Results in a Fatal Progressive Epilepsy JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2063 LP - 2074 DO - 10.1523/JNEUROSCI.18-06-02063.1998 VL - 18 IS - 6 AU - Akihiro Yamamoto AU - Hideyuki Takagi AU - Daisuke Kitamura AU - Hozumi Tatsuoka AU - Hirotake Nakano AU - Hitoshi Kawano AU - Hidehito Kuroyanagi AU - Yu-ichi Yahagi AU - Shin-ichiro Kobayashi AU - Ken-ichi Koizumi AU - Tsuyoshi Sakai AU - Ken-ichi Saito AU - Tanemichi Chiba AU - Koki Kawamura AU - Katsushi Suzuki AU - Takeshi Watanabe AU - Hiroshi Mori AU - Takuji Shirasawa Y1 - 1998/03/15 UR - http://www.jneurosci.org/content/18/6/2063.abstract N2 - Protein l-isoaspartyl methyltransferase (PIMT) is suggested to play a role in the repair of aged protein spontaneously incorporated with isoaspartyl residues. We generated PIMT-deficient mice by targeted disruption of the PIMT gene to elucidate the biological role of the gene in vivo. PIMT-deficient mice died from progressive epileptic seizures with grand mal and myoclonus between 4 and 12 weeks of age. An anticonvulsive drug, dipropylacetic acid (DPA), improved their survival but failed to cure the fatal outcome. l-Isoaspartatate, the putative substrate for PIMT, was increased ninefold in the brains of PIMT-deficient mice. The brains of PIMT-deficient mice started to enlarge after 4 weeks of age when the apical dendrites of pyramidal neurons in cerebral cortices showed aberrant arborizations with disorganized microtubules. We conclude that methylation of modified proteins with isoaspartyl residues is essential for the maintenance of a mature CNS and that a deficiency in PIMT results in fatal progressive epilepsy in mice. ER -